Rhed wrote:I read your post Inferno, and all I read is that evolutionists don't like the ENCODE's research because it disagrees with evolution. I could not find any retractions from ENCODE. What I found is the interpretations of what function means (and you agree):

"3) Much of the ENCODE hype rests on the definition of the term “function”."D

Well, I have repeated part of your earlier post to emphasise the problem that everyone (except you) noticed: there was nothing in the blog which could give a rational person that idea. Hype about how ENCODE defined "function" is not a sleight on evolution.

red wrote:Well, I have repeated part of your earlier post to emphasise the problem that everyone (except you) noticed: there was nothing in the blog which could give a rational person that idea. Hype about how ENCODE defined "function" is not a sleight on evolution.

The term "function" was a misunderstanding and deals with interpretation of what that term means. That's it. Sooner or later we will still find more and more function in non-coded DNA. Evolutionists know to far to well about hype. 99% similar to chimp; then is was 98.7%, 98.6%, 95%, and now 92%. Notice a trend? The less we are similar and know that non-coded DNA is less junk and more functional, the less believable of human-chimp evolution.

Rhed wrote:The term "function" was a misunderstanding and deals with interpretation of what that term means. That's it. Sooner or later we will still find more and more function in non-coded DNA. Evolutionists know to far to well about hype. 99% similar to chimp; then is was 98.7%, 98.6%, 95%, and now 92%. Notice a trend? The less we are similar and know that non-coded DNA is less junk and more functional, the less believable of human-chimp evolution.

You are comparing chimps and chumps.Chumps are ignorant of the fact that there is a variety of ways to calculate DNA percentages, giving different outcomes of the similarity between chimpanzees and humans. The 1.2% chimp-human distinction, for example, measures only substitutions in the base building blocks of those genes which chimpanzees and humans share. A comparison of the entire genome, however, indicates that segments of DNA have also been deleted, duplicated over and over, or inserted from one part of the genome into another. Counting these differences leads to an additional 4 to 5% distinction between the human and chimpanzee genomes.

he_who_is_nobody wrote:Intelligent design creationists are not known for their reading comprehension. I believe their poor reading comprehension comes from spending years in the Quote Mines.

Copy and paste a snippet from an ENCODE research paper that retracts the 80%.

If you are looking for a straight out retraction, you will not find it. What you will find it stuff like this:

Sandwalk wrote:Now, none of these editors and experts are ENCODE Consortium authors so it's quite possible that they have all misinterpreted the 'entrée' paper. This is the view now being suggested by the Consortium leaders (Kellis et al., 2014). They now argue that Genetic, Evolutionary, and Biochemical descriptions of "function" are all reasonable approaches to understanding junk DNA and genome composition. They now claim that just having the data available is their most important contribution and not claims about how much of the genome is functional.

In contrast to evolutionary and genetic evidence, biochemical data offer clues about both the molecular function served by underlying DNA elements and the cell types in which they act, thus providing a launching point to study differentiation and development, cellular circuitry, and human disease. The major contribution of ENCODE to date has been high-resolution, highly-reproducible maps of DNA segments with biochemical signatures associated with diverse molecular functions. We believe that this public resource is far more important than any interim estimate of the fraction of the human genome that is functional.

The implication is that they really didn't mean to say that 80% of our genome is functional. It was all a misunderstanding. They are now saying that the goal of the Consortium wasn't to discover function at all but merely to provide maps of places that might be functional, depending on your definition.

Again, work on your reading comprehension. Any honest person will see the implication of this, unless they are obtuse.

Now, see how you asked me something and I answered it? Can you do the same and address everything I (and others) have asked of you?

Rhed wrote:The term "function" was a misunderstanding and deals with interpretation of what that term means. That's it. Sooner or later we will still find more and more function in non-coded DNA. Evolutionists know to far to well about hype. 99% similar to chimp; then is was 98.7%, 98.6%, 95%, and now 92%. Notice a trend? The less we are similar and know that non-coded DNA is less junk and more functional, the less believable of human-chimp evolution.

The 80% figure is wrong (and possibly not even what the ENCODE researchers claimed).

Where ole where do I find a retraction from ENCODE about the 80%??? All I find is different interpretations of the term function. And evolutionary scientists are not happy (mega-rants and tirades actually) with the results so must disagree with the scientific results.

They're not results, they are interpretations of data. The ENCODE project did transcription mappings, that doesn't mean they found any new functions (in fact, they haven't, none of the ENCODE papers demonstrate that any new function has been found).

What you call "rants" and "tirades" are actually extremely good arguments, based on observations, that the ENCODE project's interpretations of their data is unwarranted.

You can sit there and wave your hands all you want, but you will know that this is what you are doing. You still have not even begun to address the arguments for junk.

Can any evolutionists guess what the next rescuing device will be if our genome is actually 80% functional?

Did you know that evolutionary scientists actually started out believing the entire genome was functional? The rationalization was that natural selection would get rid of stuff that isn't used because it costs energy to replicate it. Turns out on closer inspection that was wrong, and a lot more complicated than initially thought.

Gradually as the data poured in, combined with a better understanding of mutation rates and so on, what emerged was actually data and calculations that showed the entire genome could not be functional. Go back and read the fucking links I gave you to Larry Moran's explanations of these facts, particularly the "Five things you need to know if you want to participate in the junk-DNA debate". It is clear you don't know any one of those five things and you are doing cursory dismissals of the articles we link you.

Inferno wrote:I'd rather you read my blog post on the subject. I'm happy to say it was cited by Ryan T. Gregory, a researcher on the topic of the c-value paradox, as a "good resource" on the topic.Of course Larry Moran's post is better, but I think mine has a broader approach.

I read your post Inferno, and all I read is that evolutionists don't like the ENCODE's research because it disagrees with evolution. I could not find any retractions from ENCODE. What I found is the interpretations of what function means (and you agree):

"3) Much of the ENCODE hype rests on the definition of the term “function”."

And you obviously don't like ENCODE's scientific papers either:

"A further update comes from a 2013 paper in “Genome Biology and Evolution”. The paper is discussed over at Pharyngula and it basically rips into ENCODE’s papers. There’s a lot of technical stuff I needn’t cover, so I’ll limit myself to mentioning one thing: Other researchers have found only 10% true functionality, that’s 70% less than the folk over at ENCODE."

ENCODE did not find any functionality. They interpreted their transcrition mappings to be indication of function, that's it. No function was actually discovered.

Do you understand what they did? They measured the amount of transcription happening at some locus, and then if they found ANY transcription they called it "biochemically active" and then used that to say "biochemical activity" is a function.

That is obviously ridiculous, since they have no idea what that transcription is doing, if anything. Even randomly generated sequence will occasionally attract transcription factors and produce spurious transcripts.

Rhed wrote:The term you used "rips" into ENCODE" means to me "tearing apart".; in other words, don't like their papers. You and evolutionists don't like the factual results because it makes evolution nothing more than a fairytale.

False as already explained. It would help your case a lot if you could get beyond handwavey dismissals and actually try to bring arguments about to show:

A. What new functions the ENCODE project have actually discovered. B. Why the reasons stated by scientists in opposition to the ENCODE projects declarations are false.

Simply blathering about how evolutionists don't like the results isn't actually showing why their arguments are wrong. You still have all your work still ahead of you.

Rumraket wrote:No, the mechanisms are the same. Mutations, selection, drift, migration and so on. The mechanisms aren't different, their relative importance is. It has been recognized that drift players a much larger role at the genomic level than previously thought. That doesn't mean natural selection no longer exists, they are not mutually exclusive.

Natural Selection (NS) conserves traits; not create.

It would be more correct to say natural selection fixes alleles in the population.

Rhed wrote:The NS mechanism is after the fact; not before the fact.

After the fact of mutation, yes. Newly arisen mutants will be subject to selection.

The the long-term evolution experiment with E coli. Mutations produced new variation and new information that natural selection could act upon and improve the fitness of the organism in it's new environment.

That's over 600 beneficial mutations fixed in the evolving population. See, now you no longer have to lie about beneficial mutations.

Rhed wrote:To test this theory, add mutations to a genome and see how it responds, a phenomenon called Epistasis:

That's what they did in Lenski's Long-term experiment. Quoting Lenski:

Richard Lenski wrote:Fitness Unlimited

This latest paper is an interesting one because it uses our most old-fashioned assays – the kind that was the heart of the LTEE when it started, and which also formed the core of that first paper back in 1991. That is, the results are based on measurements of relative fitness, coupled with new models – both descriptive and dynamical. (Although this blog post emphasizes the descriptive model, the Science paper also presents new theory showing that the descriptive model can be derived from a dynamical model of evolution that incorporates two phenomena – clonal interference and diminishing-returns epistasis – that are known to occur in the LTEE and other studies of evolving asexual populations.)

Fitness is the central phenotype in evolutionary theory; it integrates and encapsulates the effects of all mutations and their resulting phenotypic changes on reproductive success. Fitness depends, of course, on the environment, and here we measure fitness in the same medium and other conditions as used in the LTEE. We estimate the mean fitness of a sample from a particular population at a particular generation by competing the sample against the ancestral strain, and we distinguish them based on a neutral genetic marker. Prior to the competition, both competitors have been stored in a deep freezer, then revived, and acclimated separately for several generations before they are mixed to start the assay proper. Fitness is calculated as the ratio of their realized growth rates as the ancestor and its descendants compete head-to-head under the conditions that prevailed for 500 … or 5000 … or 50,000 generations.

The exciting new result is that the fitness of these evolving bacteria shows no evidence of an upper bound or asymptote.A two-parameter power law fits the data much better than does a two-parameter hyperbolic model. According to both models, the rate of fitness increase decelerates over time, as it clearly does. However, the power-law model has no asymptote, whereas the hyperbolic model has an upper bound.

Rhed wrote:bla bla bla stuff we already know...

The contribution of epistasis to the architecture of fitness in an RNA virusRafael Sanjuán, Andrés Moya, and Santiago F. Elena

The tendency for genetic architectures to exhibit epistasis among mutations plays a central role in the modern synthesis of evolutionary biology and in theoretical descriptions of many evolutionary processes. Nevertheless, few studies unquestionably show whether, and how, mutations typically interact. Beneficial mutations are especially difficult to identify because of their scarcity. Consequently, epistasis among pairs of this important class of mutations has, to our knowledge, never before been explored. Interactions among genome components should be of special relevance in compacted genomes such as those of RNA viruses. To tackle these issues, we first generated 47 genotypes of vesicular stomatitis virus carrying pairs of nucleotide substitution mutations whose separated and combined deleterious effects on fitness were determined. Several pairs exhibited significant interactions for fitness, including antagonistic and synergistic epistasis. Synthetic lethals represented 50% of the latter. In a second set of experiments, 15 genotypes carrying pairs of beneficial mutations were also created. In this case, all significant interactions were antagonistic. Our results show that the architecture of the fitness depends on complex interactions among genome components

You should actually try to read the paper you link before you link it, instead of just quotemining the abstract:

Here, we took a direct approach for characterizing the distribution of epistatic effects (8, 9). The starting point for our experiments was a collection of 91 single-nucleotide substitution mutants of vesicular stomatitis virus (VSV) created by site-directed mutagenesis (14). In a first set of experiments, we chose 28 of these genotypes that fulfilled the following two conditions (14): (i) the genomic position to be mutated and the nucleotide incorporated were both randomly chosen, and (ii) mutations had deleterious (although nonlethal) fitness effects. We randomly picked 47 pairs of these mutants and constructed the corresponding double-mutant genotypes.

So for one of their experiments, they generate random mutations and then deliberately picked only deleterious mutations to research their epistatic interactions:

In a first set of experiments, we chose 28 of these genotypes that fulfilled the following two conditions (14): (i) the genomic position to be mutated and the nucleotide incorporated were both randomly chosen, and (ii) mutations had deleterious (although nonlethal) fitness effects. We randomly picked 47 pairs of these mutants and constructed the corresponding double-mutant genotypes.

Then they turned their attention towards another experiment, where they only picked beneficial mutatants to explore their epistatic interactions:

In a second set of experiments, we chose six genotypes for which the mutation incorporated had a beneficial fitness effect (14) and created all of the 15 possible double mutants resulting from combining these single mutations.

So actually, random mutations did in fact generate beneficial mutations, otherwise the experiment would simply not have been possible.

After having picked their beneficial mutants they turned to generate double-mutants with beneficial-only mutations to see how their interacted. What they found was that, while the double-mutant still had higher fitness than the ancestral unmutated wild-type, the double-mutant had lower fitness than the single-mutants. So while the epistatic interaction reduced the fitness effect from the individual beneficial mutations when they were both were present, it was still in fact a net fitness gain.

So while it was negative epistasis, it was a net gain in fitness over the wild-type. The double mutant would still be more fit than the wild-type with no mutations. But the single-mutant would be more fit and outcompete the double-mutant in this case.

Either case would still constitute evolution by natural selection. Thank you for bringing more evidence for evolution.

By the way, It also clearly worked in the long-term Evolution experiment with E coli. Over 600 beneficial mutations accumulated in the genome of the bacterium used over the course of 50.000 generations. If two beneficial mutations necessarily only produced negative epistasis, the long-term evolution experiment with E coli should be impossible. Yet the result is right there for you to ponder.

red wrote:Well, I have repeated part of your earlier post to emphasise the problem that everyone (except you) noticed: there was nothing in the blog which could give a rational person that idea. Hype about how ENCODE defined "function" is not a sleight on evolution.

The term "function" was a misunderstanding and deals with interpretation of what that term means. That's it. Sooner or later we will still find more and more function in non-coded DNA. Evolutionists know to far to well about hype. 99% similar to chimp

Give scientific paper that claims this.

Rhed wrote:then is was 98.7%

Give scientific paper that claims this.

Rhed wrote:98.6%

Give scientific paper that claims this.

Rhed wrote:95%

Give scientific paper that claims this.

Rhed wrote:and now 92%.

Give scientific paper that claims this.

Rhed wrote:Notice a trend? The less we are similar and know that non-coded DNA is less junk and more functional, the less believable of human-chimp evolution.

Even if the trend was true, and even if there was no junk-DNA, neither of these would entail your conclusion.

If the human-chimp genetic similarity was in fact only 70%, the corresponding human-gorilla similarity would be even less. The human-Orangutan smilarity would be even less still, the human-Macaque similarity would be still less and so on and so forth. We could still reconstruct the same tree of life with a different similarity score, we would still produce the same nesting relationships and we would still be MORE similar to chimps than anything else.

The only thing a reduced similarity score would imply was that the common ancestor either laid further back in time, or that the mutation rate had been much higher than previous estimates. That's it.

I know that both creationists, and even some evolutionists, mistakenly believe it is the mere similarity between chimps and humans that make us infer we evolved from a common ancestor. This is a mistake to think. The inference of common ancestry comes from the nesting hierachies we can construct with three or more species using comparative genetics, morphology and so on.

You make so many trivial mistakes, how many fucking corrections do I need to provide you before you decide to go and actually read up on the subject instead of trying to debate it?

If all our (and Chimpanzee) DNA was functional, why the hell would that affect the comparative relationships between our two species? I can give you two subspecies of E coli that have fully functional genomes (likely not even a single redundant base-pair), and they clearly and unambigously evolved from a common ancestor (we know this because we observed it happen in an experiment). So tell me again why the percentage of functionality of the genome should affect the inference of common descent? Is there any logic to that statement?

Rumraket wrote:If all our (and Chimpanzee) DNA was functional, why the hell would that affect the comparative relationships between our two species? I can give you two subspecies of E coli that have fully functional genomes (likely not even a single redundant base-pair), and they clearly and unambigously evolved from a common ancestor (we know this because we observed it happen in an experiment). So tell me again why the percentage of functionality of the genome should affect the inference of common descent? Is there any logic to that statement?

If I could venture a guess, it has to do with Rhed reading about the percentage of our relationship with chimpanzees going from 98% to 95% at around the same time he read about functional DNA going from ~8% to 80%. Basically a causation/correlation fallacy based off of Rhed's ignorance of genetics.

Rumraket wrote:You should actually try to read the paper you link before you link it, instead of just quotemining the abstract:

Here, we took a direct approach for characterizing the distribution of epistatic effects (8, 9). The starting point for our experiments was a collection of 91 single-nucleotide substitution mutants of vesicular stomatitis virus (VSV) created by site-directed mutagenesis (14). In a first set of experiments, we chose 28 of these genotypes that fulfilled the following two conditions (14): (i) the genomic position to be mutated and the nucleotide incorporated were both randomly chosen, and (ii) mutations had deleterious (although nonlethal) fitness effects. We randomly picked 47 pairs of these mutants and constructed the corresponding double-mutant genotypes.

So for one of their experiments, they generate random mutations and then deliberately picked only deleterious mutations to research their epistatic interactions:

In a first set of experiments, we chose 28 of these genotypes that fulfilled the following two conditions (14): (i) the genomic position to be mutated and the nucleotide incorporated were both randomly chosen, and (ii) mutations had deleterious (although nonlethal) fitness effects. We randomly picked 47 pairs of these mutants and constructed the corresponding double-mutant genotypes.

Then they turned their attention towards another experiment, where they only picked beneficial mutatants to explore their epistatic interactions:

In a second set of experiments, we chose six genotypes for which the mutation incorporated had a beneficial fitness effect (14) and created all of the 15 possible double mutants resulting from combining these single mutations.

So actually, random mutations did in fact generate beneficial mutations, otherwise the experiment would simply not have been possible.

After having picked their beneficial mutants they turned to generate double-mutants with beneficial-only mutations to see how their interacted. What they found was that, while the double-mutant still had higher fitness than the ancestral unmutated wild-type, the double-mutant had lower fitness than the single-mutants. So while the epistatic interaction reduced the fitness effect from the individual beneficial mutations when they were both were present, it was still in fact a net fitness gain.

So while it was negative epistasis, it was a net gain in fitness over the wild-type. The double mutant would still be more fit than the wild-type with no mutations. But the single-mutant would be more fit and outcompete the double-mutant in this case.

Either case would still constitute evolution by natural selection. Thank you for bringing more evidence for evolution.

Sorry but I have to be blunt. You are wrong wrong wrong. And more wrong. You are so wrong I cannot even describe it to you. (sigh...)

Where to begin? For one they used Site-Directed Mutagenesis for mutations.For the set of beneficial mutations, all changes introduced were nonsynonymous: two mutants contained one change in the N gene, three in the M gene, and one in the G gene

For two, not sure where you get this "net-gain". The tests were so bad, they even called it decompensatory epistasis!

After studying each genotype separately, eight cases showed significant antagonistic epistasis (t tests, P ≤ 0.027) but none showed synergistic epistasis. Six antagonistic cases remained significant even after correcting the significance level with Bonferroni's sequential method (17). Actually, in five of these instances, the fitness of the double mutant was even less than that of either single mutant. This particular case of antagonism between mutational fitness effects is known as decompensatory epistasis (1). Therefore, on average, a viral genotype carrying two beneficial mutations does not get the entire benefit individually associated with each mutation. Indeed, when epistasis is decompensatory, both beneficial alleles involved in the interaction cannot spread to fixation in the population, because the double mutant is less fit than each single mutant

he_who_is_nobody wrote:If I could venture a guess, it has to do with Rhed reading about the percentage of our relationship with chimpanzees going from 98% to 95% at around the same time he read about functional DNA going from ~8% to 80%. Basically a causation/correlation fallacy based off of Rhed's ignorance of genetics.

Well help a brother out. Are Humans and chimps 98% similar including the non-coding and junk DNA?

he_who_is_nobody wrote:If I could venture a guess, it has to do with Rhed reading about the percentage of our relationship with chimpanzees going from 98% to 95% at around the same time he read about functional DNA going from ~8% to 80%. Basically a causation/correlation fallacy based off of Rhed's ignorance of genetics.

Well help a brother out. Are Humans and chimps 98% similar including the non-coding and junk DNA?

Rumraket wrote:This question is also answered by Larry in the blog post you link first, at the bottom.

It includes Junk-DNA. In fact most (and I emphasize MOST, not ALL, as Larry also explains) of the differences between human and chimp are IN the junk-DNA, because the functional parts are under varying levels of purifying selection.

Rumraket wrote:This question is also answered by Larry in the blog post you link first, at the bottom.

It includes Junk-DNA. In fact most (and I emphasize MOST, not ALL, as Larry also explains) of the differences between human and chimp are IN the junk-DNA, because the functional parts are under varying levels of purifying selection.

Why do you link material you don't read?

Why not help us all out by reading our posts

I also covered it earlier, albiet definitionally, repeating from the post: there is a variety of ways to calculate DNA percentages, giving different outcomes of the similarity between chimpanzees and humans. The 1.2% chimp-human distinction, for example, measures only substitutions in the base building blocks of those genes which chimpanzees and humans share. A comparison of the entire genome, however, indicates that segments of DNA have also been deleted, duplicated over and over, or inserted from one part of the genome into another. Counting these differences leads to an additional 4 to 5% distinction between the human and chimpanzee genomes.

The first 47 rows correspond to the randomly selected deleterious mutations, whereas the last 15 rows correspond with mutations of beneficial fitness effect.

See the measured fitness of double mutants. In several cases, the net effect is still positive (but less than the fitness gain of the single-mutant. So I'm not wrong, you are wrong.

They go to great lengths to explain and define how they measure fitness.

Quantifying the Strength and Direction of Epistasis. Fitness was determined for each double mutant (W ij) as well as for their corresponding single mutants (W i and W j). Under the null hypothesis of nonepistatic effects, the expected fitness for the double mutant equals the product of the fitness estimated for each single mutation (i.e., W ij = W i W j). If deleterious mutations were to interact in a synergistic way, then the observed fitness for the double mutant would be lower than expected by multiplying the fitness of both single mutations, and hence the difference between observed and expected fitnesses would became negative. By contrast, if deleterious mutations were to interact in an antagonistic way, then the observed fitness would be larger than expected under the null hypothesis of multiplicative fitness effects, and thus the difference between observed and expected fitnesses would became positive. From this argument, a convenient way of detecting the existence (and sign) of epistasis is by computing the index εij = W ij - W i W j (1).For deleterious alleles (W i < 1 and W j < 1), synergistic epistasis is defined by εij < 0, whereas antagonistic epistasis is defined by εij > 0. For beneficial alleles (W i > 1 and W j > 1), the signs of εij must be inverted.

So a deleterious fitness effect is a value less than 1, and a beneficialt fitness effect is a value greater than 1. Exactly equal to 1 is effectively neutral. Let's look at the table in supplementary info, under "Double mutant fitness": Orange = Deleterious double mutantGreen = Beneficial double mutant.

Which merely means the combined effect of two mutations was less beneficial than the effect of a single mutation. In several cases, as you can see on the supplementary information table, the net effect of both mutations was still beneficial.

Rhed wrote:Six antagonistic cases remained significant even after correcting the significance level with Bonferroni's sequential method (17). Actually, in five of these instances, the fitness of the double mutant was even less than that of either single mutant.

But still higher than the wild-type (look at the numbers). I'm still right, you're still wrong.

Rhed wrote:This particular case of antagonism between mutational fitness effects is known as decompensatory epistasis (1). Therefore, on average, a viral genotype carrying two beneficial mutations does not get the entire benefit individually associated with each mutation. Indeed, when epistasis is decompensatory, both beneficial alleles involved in the interaction cannot spread to fixation in the population, because the double mutant is less fit than each single mutant

Yes, and I have not claimed otherwise. Suppose a double mutant arises against a background of wildtype, it will still have superior fitness compared to the unmutated wild-type in several cases.

Rhed wrote:I have to ask...did you even read the paper???

No, I have to ask, did you read the paper? The whole paper, including the supplementary information, and did you understand what you read? Apparently not.

Also, THE LONG TERM EVOLUTION EXPERIMENT WITH E COLI. Got a response to that?

You seem to have totally ignored it, and now want to extrapolate the case of evolution in a single viral experiment to generalize the effect of epistasis for all of life. You need to not just look at single cases, in single experiments, to pick out single sentences you apparently don't even understand.

Rumraket wrote:They go to great lengths to explain and define how they measure fitness.

Quantifying the Strength and Direction of Epistasis. Fitness was determined for each double mutant (W ij) as well as for their corresponding single mutants (W i and W j). Under the null hypothesis of nonepistatic effects, the expected fitness for the double mutant equals the product of the fitness estimated for each single mutation (i.e., W ij = W i W j). If deleterious mutations were to interact in a synergistic way, then the observed fitness for the double mutant would be lower than expected by multiplying the fitness of both single mutations, and hence the difference between observed and expected fitnesses would became negative. By contrast, if deleterious mutations were to interact in an antagonistic way, then the observed fitness would be larger than expected under the null hypothesis of multiplicative fitness effects, and thus the difference between observed and expected fitnesses would became positive. From this argument, a convenient way of detecting the existence (and sign) of epistasis is by computing the index εij = W ij - W i W j (1).For deleterious alleles (W i < 1 and W j < 1), synergistic epistasis is defined by εij < 0, whereas antagonistic epistasis is defined by εij > 0. For beneficial alleles (W i > 1 and W j > 1), the signs of εij must be inverted.

So a deleterious fitness effect is a value less than 1, and a beneficialt fitness effect is a value greater than 1. Exactly equal to 1 is effectively neutral. Let's look at the table in supplementary info, under "Double mutant fitness": Orange = Deleterious double mutantGreen = Beneficial double mutant.

Rumraket wrote:Which merely means the combined effect of two mutations was less beneficial than the effect of a single mutation. In several cases, as you can see on the supplementary information table, the net effect of both mutations was still beneficial.

Rhed wrote:Six antagonistic cases remained significant even after correcting the significance level with Bonferroni's sequential method (17). Actually, in five of these instances, the fitness of the double mutant was even less than that of either single mutant.

Rumraket wrote:But still higher than the wild-type (look at the numbers). I'm still right, you're still wrong.

Rhed wrote:This particular case of antagonism between mutational fitness effects is known as decompensatory epistasis (1). Therefore, on average, a viral genotype carrying two beneficial mutations does not get the entire benefit individually associated with each mutation. Indeed, when epistasis is decompensatory, both beneficial alleles involved in the interaction cannot spread to fixation in the population, because the double mutant is less fit than each single mutant

Rumraket wrote:Yes, and I have not claimed otherwise. Suppose a double mutant arises against a background of wildtype, it will still have superior fitness compared to the unmutated wild-type in several cases.

Rhed wrote:I have to ask...did you even read the paper???

Rumraket wrote:No, I have to ask, did you read the paper? The whole paper, including the supplementary information, and did you understand what you read? Apparently not.

I read the whole thing. I understood it. But to make sure I went back to see if I missed something or you missed something. I believe I found the error. There is a section in the paper named Epistasis Among Pairs of Beneficial Mutations under The Results:

"Epistasis Among Pairs of Beneficial Mutations. Let us now move our attention to the 15 genotypes carrying two mutations for which the expected fitness effect was beneficial. The average epistatic effect, Formula, was also significantly antagonistic (Fig. 2; t 14 = 4.522, P < 0.001) and the distribution of epistatic interactions was effectively symmetrical (Fig. 2; g 1 = -0.304 ± 0.580; t 14 = 0.524, P = 0.608) and unimodal as well (Fig. 2; g 2 = -0.576 ± 1.121; t 14 = 0.514, P = 0.616). However, the conclusion of a predominance of antagonistic epistasis between pairs of beneficial mutations can be jeopardized by a lack of statistical independence among the 15 genotypes used in this experiment. We created all possible double mutants from six beneficial mutations, but this set of double mutants does not represent a random sample of all possible double mutants on the genome, because several genotypes contain the same mutation. To circumvent this statistical problem, we used a bootstrap approach. One thousand size six random samples were taken from the original dataset, and a Formula value was computed from each sample. Samples of size six were taken simply because six is the number of independent mutations from which the experiment was initiated. The 95% bootstrap confidence interval for Formula ranged between -0.129 and -0.087, slightly more negative than computed above. (The conclusion was completely robust to changes in the sample sizes used during the bootstrap resampling, because 14 of 15 cases had ε < 0.) This result gives even more strength to our conclusion of a predominance of antagonistic epistasis among beneficial mutations. "

They used the bootstrap approach. I knew something was odd with your analyses with the numbers and with the conclusions of the research paper. The observed expected fitness was less than 0. Beneficial mutations had a antagonic epistasis effect. Not one did a beneficial mutation had a synergistic epistasis effect (a requirement for evolution to work). And I quote, "Therefore, on average, a viral genotype carrying two beneficial mutations does not get the entire benefit individually associated with each mutation. Indeed,when ipistasis is decompensatory, both beneficial alleles involved in the interaction cannot spread to fixation in the population".

Rumraket wrote:Also, THE LONG TERM EVOLUTION EXPERIMENT WITH E COLI. Got a response to that?

You seem to have totally ignored it, and now want to extrapolate the case of evolution in a single viral experiment to generalize the effect of epistasis for all of life. You need to not just look at single cases, in single experiments, to pick out single sentences you apparently don't even understand.

"But this is irrelevant because in either case, whether a god exists or not, whether your God (with a capital G) exists or not, it doesn't matter. We both are, in either case, evolved apes. " - Nesslig20

I wondered why you'd quote my entire post without responding to it, then I noticed you've just failed to use the quote function properly and saw you had a small response in there. Full of errors, so here goes:

Rhed wrote:They used the bootstrap approach. I knew something was odd with your analyses with the numbers and with the conclusions of the research paper.

There's nothing wrong with my analysis, because it isn't an analysis. It is a direct reading of the paper as-is. The numbers are right there, they unambiguously state their methodology.

Rhed wrote: The observed expected fitness was less than 0.

There is no such thing as "observed expected fitness".

There is expected fitness (which is calculated beforehand using the fitness of two single mutants)andObserved fitness (which is the observed fitness of single and double-mutant carriers) (Wi is mutant one, Wj is mutant two, Wij is a double-mutant carrying the mutations of both Wi and Wj)

The two are compared.

The expected fitness is computed from an assumption of multiplicative epistatic interactions (they explain this in the paper, you clearly didn't understand it). That simply means they expect the fitness of a double mutant to be the product of two individual single-mutants.

So if mutant-i has a fitness of 0.8 (a deleterious mutation, since Wi <1)And if mutant-j has a fitness of 0.8 tooThe product would be 0.8*0.8 = 0.68The product would then be the expected fitness, Wexpected.

So the expectation is that for deleterious mutations in combination, the result should be an organism that is less fit than either single mutant (We < Wi or Wj). So if the observed fitness of the double mutant is less than the observed fitness of either single mutant, the epistatic effect is called antagonistic.

This is also true for beneficial mutations:So if mutant-i has a fitness of 1.01 (a beneficial mutation, since Wi >1)and if mutant-j has a fitness of 1.01 tooThe product would be 1.01*1.01 = 1.02The product would then be the expected fitness, Wexpected.

So the expectation is that for double beneficial mutations, the result should be an even more fit organism than either single mutant. Since obviously the expected product is greater than either of the two single mutants (1.01) and trivially 1.02>1.01, the expectation is synergistic epistasis for double beneficial mutations.

So if the observed fitness (suppose it was 1.005) of the double mutant, is less than the either single mutant (1.01), then the epistatic effect is called antagonistic (assumes Wij expected < Wi or Wj).

But notice, the total fitness of the double mutant can STILL be antagonistic and be above 1.0.As long as it is below the expectation of 1.02, and above neutral (1.0), it is beneficial but antagonistic.

Why do I have to explain all this stuff to you? It is elementary fucking arithmetic.

Rhed wrote: Beneficial mutations had a antagonic epistasis effect.

Yes, because in all cases the observed fitness was less than the product of the two single mutants. But in several cases it was still beneficial, because it still had a fitness above 1.0

LOOK AT THE NUMBERS, THEY ARE FROM THE PAPER, THEY ARE NOT AN "ANALYSIS".

Rhed wrote:Not one did a beneficial mutation had a synergistic epistasis effect

Correct, none of the double mutants using beneficial mutations had synergistic epistatic effects. But several of them were still beneficial (Wij > 1).

Also, several double deleterious mutants had both synergistic epistatic effects and were beneficial. The fitness of the double mutant was higher than either single mutant, and it was greater than 1. Look at the numbers in the supplementary information.

The fitness of the double mutant is above 1, despite both of the single mutations being deleterious (fitness < 1). Well fuck me, that's synergistic epistasis right there.

Rhed wrote:(a requirement for evolution to work).

False. A beneficial double mutant can arise against a background of wildtype, with no higher-fitness single mutants being present. The likelihood of this is of course less than the likelihood that a beneficial single-mutant will also arise in the population.

Also, a double mutant can arise against a background of single mutants, but then become geographically isolated and rise to fixation.

Rhed wrote:And I quote, "Therefore, on average a viral genotype carrying two beneficial mutations does not get the entire benefit individually associated with each mutation.

And there we have it, you missed the key word. On average.

The total average effect of all double mutants was antagonistic, because the observed fitness was lower than the observed fitness of either single mutant

IT WAS HOWEVER STILL SYNERGISTIC (Wij > Wi or Wj) IN SOME FEW CASES FOR DOUBLE DELETERIOUS MUTANTS, AND STILL BENEFICIAL (Wij >1) IN SEVERAL MORE.

Rhed wrote:Indeed, when epistasis is decompensatory, both beneficial alleles involved in the interaction cannot spread to fixation in the population".

Because their combination is less fit than their product, but this simply implies both single mutants are present, instead of a scenario where a double mutant arises against a background of no beneficial single mutants.